Schizophrenia is a common serious mental illness, and is the most serious and damaging kind in all mental illness. The worldwide incidence of schizophrenia is about 1%, and has a significant increasing trend with the environmental deterioration and the increasing living pressure. Most patients with schizophrenia give up treatment due to long treatment cycle, high treatment cost and big side effects, which lead to more severe social consequences.
A large number of studies have shown that a dopamine system of the brain is closely related to human's normal mental activities. A disorder of the dopamine system can lead to a variety of psychoneuroses such as schizophrenia, neuropathic pain, mania, anxiety disorder, all kinds of depression, Parkinson's disease, etc. Of the above diseases, schizophrenia has the closest relation to dopaminergic system.
Traditional antipsychotic drugs (such as dopamine D2 receptor antagonists) and non-typical antipsychotic drugs (such as D2/5-HT dual antagonists) are clinically used at the moment, wherein traditional antipsychotic drugs have been eliminated gradually since they cause extrapyramidal symptoms (EPS) easily. There are many types of non-typical antipsychotic drugs, whereas none of them is prominent in improving the entire schizophrenia spectrum, and most of them only improve a syndrome in positive or negative symptoms or reduce side effects. Therefore, finding a novel anti-schizophrenia medicament having a low side effect, rapid onset of action and a broad spectrum of treatment is always a focus among the worldwide pharmaceutical industries.
In recent years, scientists have found that partial dopamine receptor agonists can reduce rather than completely block the transmission of dopamine in dopamine over-activity, while cause excitement when dopaminergic activity is low on the contrary. The partial dopamine receptor agonists have a significant treatment effect on both positive and negative symptoms of the mental illness, and reduce reoccurrence of schizophrenia and improve emotion and cognitive dysfunction if administrated in long-term use. The EPS side effect and the action of increasing a level of prolactin in serum are smaller than both traditional antipsychotic drugs and non-typical antipsychotic drugs. Therefore, a novel anti-schizophrenia medicament having a function of partial agonization of dopamine D2 receptor is a focus and an important development target of the current research.
The aralkyl substituted piperidine or piperazine derivative of the present invention can stabilize the dopaminergic system of the brain, and show potential for treating and improving a variety of psychoneuroses, and can be used for the treatment of neuropathic pain, mania, schizophrenia, anxiety disorder, all kinds of depressions. Parkinson's disease, in particularly schizophrenia.